Globally, children who acquire HIV-1 increasingly do so in the context of maternal antiretroviral prophylaxis. It is important to determine whether maternal antiretroviral prophylaxis should alter infant treatment regimens. Nevirapine (NVP) is commonly used for PMTCT and is also a commonly used first-line drug for treatment of pediatric HIV-1. Approximately half of infants exposed to NVP have detectable NVP resistance early in infancy, with loss of detectable resistance over time. Thus, if an HIV-1 infected child was exposed to single-dose NVP prophylaxis, the question remains whether NVP or any NNRTI can be used effectively in therapeutic regimens. Alternative PI-based regimens are associated with heat-lability, poor palatability, cumulative toxicity, and fewer salvage options. This poses challenges for pediatric PI-based highly active antiretroviral therapy (HAART) in settings without refrigeration and limited antiretroviral repertoire. It is plausible that in older NVP-exposed infants (older than 6 months since exposure) who are genotypically NVP-susceptible, that nevirapine will be effective and useful.

We propose to study resistance in a pediatric HIV-1 clinical trial involving 100 children. Among children enrolled at between 6 and 18 months of age, we will provide real-time field-based genotypic NVP-resistance testing, and randomize 100 NVP-susceptible children to NVP-containing versus NVP-sparing HAART to compare therapeutic response, adverse events, and morbidity in the 2 arms during 2-year follow-up. Follow-up in these studies will be closely monitored by an external Data Safety and Monitoring Board (DSMB).

Incidence of mortality will be compared in NVP-containing and NVP-sparing arms at every monthly visit following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: No ]

CD4% will be compared in NVP-containing and NVP-sparing arms at every 3-monthly intervals following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: No ]

Viral suppression in NVP-containing and NVP-sparing arms will be compared at 3, 6 and then every 6 monthly intervals following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of severe adverse events will be compared in NVP-containing and NVP-sparing arms at every monthly visit following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: Yes ]

Correlates of toxicities will be compared in NVP-containing and NVP-sparing arms at every monthly visit following randomization [ Time Frame: Over 24 months of post-randomization follow-up ] [ Designated as safety issue: Yes ]

Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.

Infant has received any prior antiretroviral therapy (expect prophylaxis for PMTCT)

Infant has evidence of active tuberculosis

Mother currently receiving NVP-containing HAART and breastfeeding the infant

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00427297